Murine Guanylate Binding Protein 2 (mGBP2) controls Toxoplasma gondii replication

作者：Degrandi Daniel; Kravets Elisabeth; Konermann Carolin; Beuter Gunia Cornelia; Kluempers Verena; Lahme Sarah; Wischmann Eva; Mau**erg Anne K; Beer Hammer Sandra; Pfeffer Klaus^*

来源：Proceedings of the National Academy of Sciences, 2013, 110(1): 294-299.

DOI：10.1073/pnas.1205635110

• pathogen defense
• cell-autonomous immunity
• host-pathogen interaction

IFN-gamma orchestrates the host response against intracellular pathogens. Members of the guanylate binding proteins (GBP) comprise the most abundant IFN-gamma-induced transcriptional response. mGBPs are GTPases that are specifically up-regulated by IFN-gamma, other proinflammatory cytokines, toll-like receptor agonists, as well as in response to Listeria monocytogenes and Toxoplasma gondii infection. mGBP2 localizes at the parasitophorous vacuole (PV) of T. gondii; however, the molecular function of mGBP2 and its domains in T. gondii infection is not known. Here, we show that mGBP2 is highly expressed in several cell types, including T and B cells after stimulation. We provide evidence that the C-terminal domain is sufficient and essential for recruitment to the T. gondii PV. Functionally, mGBP2 reduces T. gondii proliferation because mGBP2-deficient cells display defects in the replication control of T. gondii. Ultimately, mGBP2-deficient mice reveal a marked immune susceptibility to T. gondii. Taken together, mGBP2 is an essential immune effector molecule mediating antiparasitic resistance.

• 出版日期2013-1-2
• 单位河北医科大学